There is a critical need to develop an affordable, non-ionizing, three-dimensional (3-D) quantitative imaging modality for screening women who are at higher risk for breast cancer and monitoring changes in breast tissue properties in response to treatment protocols. Given increasing recognition of the importance of breast density in individualized risk assessment and prevention decisions, there is also an emerging need to develop such a modality for evaluating breast density in the general population and monitoring changes in density in response to preventative interventions. 3-D microwave imaging - a non-ionizing molecular imaging technique that senses the endogenous (and possibly exogenously influenced) dielectric properties of breast tissue - has great potential to meet these needs. The long-term goal is to develop and integrate microwave imaging into the arsenal of tools available to the breast care clinician. The objective of this project, which is directed toward achieving this long-term goal, is to develop and evaluate a 3-D quantitative microwave imaging system based on advanced sensor hardware, algorithms, and computational platforms and to demonstrate the feasibility of performing a rigorous validation of microwave imaging against breast MRI, a clinical 3-D benchmark. The following specific aims will be pursued to achieve this objective: 1) Construct a compact, efficient 3-D microwave sensor system that enables co-registration with MRI; 2) Develop computationally efficient high- resolution 3-D microwave imaging algorithms that are integrated with the hardware system; and 3) Conduct a small-scale proof-of-concept imaging study with human research subjects. The project is innovative both in terms of the clinical applications and the technical approach. First, breast density evaluation and contrast- enhanced detection of breast cancer represent two new directions for microwave imaging. Second, our non- invasive quantitative microwave imaging system will employ efficient multi-band miniaturized antennas in a dense 3-D array and multi-frequency, physiologically constrained, 3-D inverse scattering algorithms. Most importantly, an innovative system configuration will maintain the position of the breast during both the MRI (benchmark) and microwave (test) scans, enabling an objective and unambiguous validation of microwave breast imaging. The proposed research is significant because it is expected to provide clinical evidence of the efficacy of 3-D microwave breast imaging and ultimately yield an affordable, widely available, and safe imaging solution for automated, quantitative breast density evaluation in the general population and cancer screening in a currently underserved sub-population of women who are known to be at higher risk.